Regulation of glucose transporters in cultured rat adipocytes: synergistic effect of insulin and dexamethasone on GLUT4 gene expression through promoter activation
A triggering effect of insulin on GLUT4 expression in adipocytes is consistently observed in vivo, whereas GLUT1 is roughly unaffected. However, in cultured rat adipocytes, insulin increases GLUT1 but fails to increase GLUT4, suggesting that additional factors are involved in vivo. This prompted us...
Saved in:
Published in | Endocrinology (Philadelphia) Vol. 136; no. 11; p. 4782 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.11.1995
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | A triggering effect of insulin on GLUT4 expression in adipocytes is consistently observed in vivo, whereas GLUT1 is roughly unaffected. However, in cultured rat adipocytes, insulin increases GLUT1 but fails to increase GLUT4, suggesting that additional factors are involved in vivo. This prompted us to evaluate the potential role of glucocorticoids as coregulators with insulin of glucose transporter expression using 3T3-F442A adipose cells and primary cultured rat adipocytes. In both systems, insulin increased and dexamethasone decreased GLUT1 messenger RNA (mRNA) and protein, an effect inhibited by the glucocorticoid antagonist RU 38486. When the two hormones were added together, the effect of dexamethasone was dominant in 3T3-F442A cells, but was totally antagonized in rat adipocytes. Moreover, in rat adipocytes, the GLUT1 gene transcription rate (run-on) was identical in the absence or presence of the two hormones. With regard to GLUT4 expression, neither insulin nor dexamethasone alone had any significant effect after 2 days of treatment. In contrast, the combined hormones markedly increased GLUT4 mRNA (+550% in rat adipocytes; +130% in 3T3-F442A cells) and protein (+164% in rat adipocytes; +79% in 3T3-F442A cells) with a 24- to 48-h delay after mRNA induction. Studies of the molecular mechanism(s) showed that exposure of rat adipocytes to dexamethasone plus insulin did not affect GLUT4 mRNA stability, but increased the GLUT4 gene transcription rate 3-fold. Transient transfections of rat adipocytes with the 5'-flanking 2.2-kilobase sequence of the rat GLUT4 gene fused to luciferase demonstrated that promoter activity was unchanged by insulin, increased 50% by dexamethasone, and increased 3-fold in the presence of both. These data show that insulin elicits an increase in GLUT4 gene expression provided glucocorticoids are present. Our results indicate that the synergism between insulin and glucocorticoids on GLUT4 gene transcription is mediated through GLUT4 promoter activation. |
---|---|
AbstractList | A triggering effect of insulin on GLUT4 expression in adipocytes is consistently observed in vivo, whereas GLUT1 is roughly unaffected. However, in cultured rat adipocytes, insulin increases GLUT1 but fails to increase GLUT4, suggesting that additional factors are involved in vivo. This prompted us to evaluate the potential role of glucocorticoids as coregulators with insulin of glucose transporter expression using 3T3-F442A adipose cells and primary cultured rat adipocytes. In both systems, insulin increased and dexamethasone decreased GLUT1 messenger RNA (mRNA) and protein, an effect inhibited by the glucocorticoid antagonist RU 38486. When the two hormones were added together, the effect of dexamethasone was dominant in 3T3-F442A cells, but was totally antagonized in rat adipocytes. Moreover, in rat adipocytes, the GLUT1 gene transcription rate (run-on) was identical in the absence or presence of the two hormones. With regard to GLUT4 expression, neither insulin nor dexamethasone alone had any significant effect after 2 days of treatment. In contrast, the combined hormones markedly increased GLUT4 mRNA (+550% in rat adipocytes; +130% in 3T3-F442A cells) and protein (+164% in rat adipocytes; +79% in 3T3-F442A cells) with a 24- to 48-h delay after mRNA induction. Studies of the molecular mechanism(s) showed that exposure of rat adipocytes to dexamethasone plus insulin did not affect GLUT4 mRNA stability, but increased the GLUT4 gene transcription rate 3-fold. Transient transfections of rat adipocytes with the 5'-flanking 2.2-kilobase sequence of the rat GLUT4 gene fused to luciferase demonstrated that promoter activity was unchanged by insulin, increased 50% by dexamethasone, and increased 3-fold in the presence of both. These data show that insulin elicits an increase in GLUT4 gene expression provided glucocorticoids are present. Our results indicate that the synergism between insulin and glucocorticoids on GLUT4 gene transcription is mediated through GLUT4 promoter activation. |
Author | Hajduch, E Guerre-Millo, M Meunier, C Hainault, I Jardel, C Hainque, B Lavau, M |
Author_xml | – sequence: 1 givenname: E surname: Hajduch fullname: Hajduch, E organization: INSERM U-177, Institut Biomédical des Cordeliers, Paris, France – sequence: 2 givenname: I surname: Hainault fullname: Hainault, I – sequence: 3 givenname: C surname: Meunier fullname: Meunier, C – sequence: 4 givenname: C surname: Jardel fullname: Jardel, C – sequence: 5 givenname: B surname: Hainque fullname: Hainque, B – sequence: 6 givenname: M surname: Guerre-Millo fullname: Guerre-Millo, M – sequence: 7 givenname: M surname: Lavau fullname: Lavau, M |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/7588207$$D View this record in MEDLINE/PubMed |
BookMark | eNotkFFLwzAUhfMwmXP66puQP9Ca3GZL65sMncJAkO15pO1NF2mTkqSy_R7_qJ3u6XAO3PMd7g2ZWGeRkHvOUg6cPaJNebZMOU-FzGFCZozxLJEA8prchPA1WiFENiVTuchzYHJGfj6xGVoVjbPUadq0Q-UC0uiVDb3zEX2gxtJqaOPgsaZeRapq07vqFDE80XCy6BsToqkoao1VPNcYG4Z2PFO2pjUeVYfxoMI4lo6Y9Wa3FbTB0eGx9xjCGR4P3g3NgfbedW7EUlVF8_037JZcadUGvLvonOxeX7art2TzsX5fPW-SCnKICRcZE1qpUkhgWnAOSoOCfLnAMa51WRasEMgKiQLEslASpOBQL8pClsgkzMnDf28_lB3W-96bTvnT_vIs-AW9DHAy |
CitedBy_id | crossref_primary_10_1038_oby_2000_60 crossref_primary_10_1111_j_1365_201X_2004_01384_x crossref_primary_10_1016_j_cca_2009_06_030 crossref_primary_10_1089_jmf_2012_2583 crossref_primary_10_1016_S0014_5793_03_00773_7 crossref_primary_10_1016_j_domaniend_2004_12_003 crossref_primary_10_1016_S0014_5793_01_02353_5 crossref_primary_10_1530_JOE_11_0359 crossref_primary_10_1111_j_1439_0396_2011_01180_x |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1210/en.136.11.4782 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine Anatomy & Physiology |
ExternalDocumentID | 7588207 |
Genre | Journal Article |
GroupedDBID | --- -DZ -~X .55 .GJ .XZ 08P 0R~ 18M 1TH 29G 2WC 34G 354 39C 3O- 3V. 4.4 48X 53G 5GY 5RE 5RS 5YH 79B 8F7 AABZA AACZT AAIMJ AAJQQ AAKAS AAPGJ AAPQZ AAPXW AARHZ AAUAY AAUQX AAVAP AAWDT AAYJJ ABEFU ABHFT ABJNI ABLJU ABMNT ABNHQ ABPPZ ABPQP ABPTD ABQNK ABSAR ABWST ABXVV ACFRR ACGFO ACGFS ACIPB ACIWK ACPRK ACUTJ ACZBC ADBBV ADGKP ADGZP ADHKW ADIYS ADQBN ADRTK ADVEK ADZCM AELWJ AEMDU AENEX AENZO AETBJ AEWNT AFFNX AFFZL AFGWE AFOFC AFRAH AFULF AFXAL AFYAG AGINJ AGKRT AGMDO AGQXC AGUTN AHMBA AJEEA ALMA_UNASSIGNED_HOLDINGS APIBT APJGH AQKUS ARIXL ATGXG AVNTJ BAWUL BAYMD BCRHZ BENPR BEYMZ BPHCQ BSWAC BTRTY BVXVI C1A C45 CDBKE CGR CJ0 CS3 CUY CVF DAKXR DIK DU5 E3Z EBS ECM EIF EJD EMOBN ENERS F5P FA8 FECEO FHSFR FLUFQ FOEOM FOTVD FQBLK GAUVT GJXCC GX1 H13 HF~ HZ~ H~9 IAO IH2 IHR ITC J5H KBUDW KOP KQ8 KSI KSN L7B LMP M5~ MBLQV MHKGH MJL MVM NLBLG NOMLY NOYVH NPM NVLIB O9- OAUYM OBH ODMLO OFXIZ OHH OHT OJZSN OK1 OPAEJ OVD OVIDX P2P PQQKQ PROAC Q-A REU ROX ROZ TEORI TJX TLC TMA TR2 TWZ UPT VQP VVN W2D W8F WH7 WHG WOQ X52 X7M XJT XOL YBU YHG YOC YQI YSK YYP ZCA ZCG ZGI ZKB ZXP ZY1 |
ID | FETCH-LOGICAL-c282t-14304faab4720f4112af2a2865e4fadfbb9094e097e42469a727412d5b97be072 |
ISSN | 0013-7227 |
IngestDate | Sat Sep 28 07:35:06 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 11 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c282t-14304faab4720f4112af2a2865e4fadfbb9094e097e42469a727412d5b97be072 |
PMID | 7588207 |
ParticipantIDs | pubmed_primary_7588207 |
PublicationCentury | 1900 |
PublicationDate | 1995-11-01 |
PublicationDateYYYYMMDD | 1995-11-01 |
PublicationDate_xml | – month: 11 year: 1995 text: 1995-11-01 day: 01 |
PublicationDecade | 1990 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Endocrinology (Philadelphia) |
PublicationTitleAlternate | Endocrinology |
PublicationYear | 1995 |
SSID | ssj0014443 |
Score | 1.7082682 |
Snippet | A triggering effect of insulin on GLUT4 expression in adipocytes is consistently observed in vivo, whereas GLUT1 is roughly unaffected. However, in cultured... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 4782 |
SubjectTerms | Adipocytes - metabolism Animals Cell Line Cell Nucleus - metabolism Dexamethasone - pharmacology Drug Synergism Gene Expression Regulation Glucose Transporter Type 1 Glucose Transporter Type 4 Insulin - pharmacology Kinetics Luciferases - genetics Monosaccharide Transport Proteins - genetics Muscle Proteins Promoter Regions, Genetic Rats Recombinant Fusion Proteins RNA, Messenger - metabolism Transcription, Genetic Transfection |
Title | Regulation of glucose transporters in cultured rat adipocytes: synergistic effect of insulin and dexamethasone on GLUT4 gene expression through promoter activation |
URI | https://www.ncbi.nlm.nih.gov/pubmed/7588207 |
Volume | 136 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwELW2IFAvCFoqvjUHxAWlSrJOnHCrqkKF2B7QrtRb5cS2WKRmo5JF3f4dfgh_jRnbiXcXEB-XaGVH3iTzNBlP3rxh7GWhagwaeBllhlqYmbKM8K0occ9juMpkkQtN1ciTs_x0xt-fZ-ej0fc11tKyqw7rm1_WlfyPVXEM7UpVsv9g2WFRHMDfaF88ooXx-Fc2_ugayfuYr2efd4Ne-ZUluzpxDQws0divpZq3i3rVOSrclxWV_lmtZs_scBISjp9OOXWlryV1mZYYl2v6svDuw2zKqfGypu4AjkXbDO1-Wsvu01dWo-NrsHqf-2_UAt2Uy-VTcEv5HBKqbD8RabcM_vCzWromVSdhbN5IvJWNVO9EL5u5r2UcyEAIesc9OA45DVsjngw5De-nk3EkUqcaMPhpp5TSAzJZc7tcuA5GP70PcENrkUFsPnw7HG6fiI-6vbTowH0TBkPij5Nb6tx-ZoftiIIc7Bkli_xHLM49adPfjNcMpaKpzSvaZXf8OlubGxvkTO-ze353AkcOag_YSDd7bP-okd3icgWvwPKFrfH22N2Jp2Xss28BiLAw4IEI60CEeQM9EAGBCAGIb2ANhuBgSMt4GALCEDZgCPg3FoZAMIQAQ_AwhB6GEGD4kM3enkyPTyPf_SOq0yLtIgzkY26krLhIY8NxXyBNKqmQWuOwMlVVxiXXcSk0T3leSkFKTKnKqlJUOhbpAbvV4DU9YiAyVXGdZ3Uiay4LU-lxXhfCSDE2ItH5Y3bgnvpF6yReLrw5nvxu4inbDbh9xm4b9Cj6OYanXfXCguAHp5qWPg |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Regulation+of+glucose+transporters+in+cultured+rat+adipocytes%3A+synergistic+effect+of+insulin+and+dexamethasone+on+GLUT4+gene+expression+through+promoter+activation&rft.jtitle=Endocrinology+%28Philadelphia%29&rft.au=Hajduch%2C+E&rft.au=Hainault%2C+I&rft.au=Meunier%2C+C&rft.au=Jardel%2C+C&rft.date=1995-11-01&rft.issn=0013-7227&rft.volume=136&rft.issue=11&rft.spage=4782&rft_id=info:doi/10.1210%2Fen.136.11.4782&rft_id=info%3Apmid%2F7588207&rft_id=info%3Apmid%2F7588207&rft.externalDocID=7588207 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0013-7227&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0013-7227&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0013-7227&client=summon |